1. Field
Provided is an anti-Ang2 antibody or an antigen-binding fragment thereof that specifically binds to an angiogenesis-inducing factor Angiopoietin-2 (Ang2) and complexes with a Tie2 receptor while bound to Ang2, and a method for enhancing an efficacy of an anticancer agent, and a use thereof for combination therapy for treating a cancer.
2. Description of the Related Art
Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2) bind to Tie2 receptor specifically expressed in vascular endothelial cells, thereby performing complicated functions in angiogenesis and vascular remodeling.
Angiopoietin-1 (Ang1) is a ligand which is thought to activate the Tie2 receptor, relate to the formation and maturation of blood vessels, and contribute to vascular stabilization by increasing interaction between vascular endothelial cells and pericytes. In addition, it is believed that Ang1 functions as a key regulator for maintaining the stabilization of blood vessels by maintaining the barrier function of vascular endothelial cells. The vascular endothelial cells are activated in the status of the overexpression of VEGF or inflammation, and vascular permeability is increased. Ang1 induces the stabilization of vascular endothelial cells and reduces vascular permeability by accelerating the junctional integrity of the vascular endothelial cells.
The overexpression of Ang2 in a variety of solid cancers and blood cancers has been reported, and Ang2 expression in a serum often serves as a biomarker of poor prognosis of anticancer therapy. The overexpression of Ang2 has been reported not only in the cancers but also in various diseases including sepsis, bacterial infection, lung injury, kidney injury, etc. Such overexpressed Ang2 is thought to inhibit stabilization of vascular endothelial cells by competing with Ang1. Due to such correlation with such pathological conditions, Ang2 has been considered to be a target in therapeutic intervention. Currently, a variety of drugs targeting Ang2 are currently in the clinical or preclinical stages of development, and they have a variety of forms including a peptibody, bispecific antibody, monoclonal antibody, etc.
However, most of the Ang2-target drugs prevent Ang2 from binding to the Tie2 receptor.